PROJECT SUMMARY/ABSTRACT Neurological complications of SARS-CoV2 or Covid-19 have been reported in the literature but little is known about the extent to which neural systems are affected by this disease or the long-term impact on brain function. Alcohol consumption during the Covid-19 pandemic is on the rise due to factors such as unemployment, financial strain, and loss of social support and may be a significant risk factor for neurological complications of SARS- CoV2. Other coronaviruses such as SARS-CoV are thought to gain entry to the brain via the olfactory bulb and quickly spread to interconnected regions such as the dorsal raphe nucleus (DRN), which is a major source of serotonin (5-HT) neurons in the brain that orchestrates neurological functions ranging from autonomic control to emotional and motivated behavior. Alcohol is also known to compromise the function of 5-HT neurons in the brain and may render them more vulnerable to infection by SARS-CoV2, exacerbating the neuropsychiatric sequelae of this disease. The goal of the present application is to determine whether alcohol can increase expression of known entry factors for SARS-CoV2 in DRN 5-HT neurons and facilitate infection of these neurons. In Aim 1, we will determine whether chronic intermittent alcohol exposure upregulates expression of entry factors ACE2 and TMPRSS2 in 5-HT DRN neurons that project to the olfactory bulb using retrograde tracers. In Aim 2, we will determine whether SARS-CoV2 can infect 5-HT DRN neurons via the olfactory bulb and whether chronic intermittent alcohol exacerbates infection and death of these neurons. Together, these studies will reveal whether alcohol is a significant risk factor for SARS-CoV2 invasion of the CNS and whether the DRN 5-HT systems is a target for this infection.